Reaching the Holy Grail: Making Hematopoietic Stem Cells in a Dish

The successful generation of long-term engrafting hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (hiPSCs) has long been sought to revolutionize treatments for hematological disorders, eliminating reliance on donors and avoiding immune rejection, and thus has been seen as a major milestone in regenerative medicine. Previous studies, guided by developmental hematopoiesis, made progress in creating blood cells from hiPSCs, but challenges persisted in producing hematopoietic cells with functional properties of genuine HSCs capable of long-term engraftment. In their recent study, Ng and colleagues described an optimized differentiation protocol that manipulates key signaling pathways, including TGF-β, WNT, BMP, and retinoic acid in a stage-specific manner to generate HSCs with multilineage capacity. This strategy yielded hematopoietic cells capable of engrafting long term with high levels of human chimerism in recipient mice. This research provides a blueprint for future studies aiming for personalized HSC-based therapies for various blood disorders.